Beneficial chromosomal integration of the genes for CTX-M extended-spectrum β-Lactamase in klebsiella pneumoniae for stable propagation

Eun Jeong Yoon, Bareum Gwon, Changseung Liu, Dokyun Kim, Dongju Won, Sung Gyun Park, Jong Rak Choi, Seok Hoon Jeong

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19 Citations (Scopus)


The acquired CTX-M-type extended-spectrum-β-lactamase (ESBL)-producing Enterobacterales are of great concern in clinical settings because they limit therapeutic options for patients infected by the pathogens. An intriguing clonality of CTX-M ESBL-producing Klebsiella pneumoniae blood isolates was observed from a national cohort study, and comparative genomics were assessed for the 115 K. pneumoniae blood isolates carrying the blaCTX-M gene. The plasmid preference of particular clones of a sequence type (ST) was assessed by liquid mating. A quarter of the blaCTX-M gene-carrying K. pneumoniae blood isolates harbor the gene in their chromosome, and most of those with the built-in blaCTX-M gene belonged either to ST307 or ST48. Notably, all 16 K. pneumoniae ST48 isolates harbored two copies of the blaCTX-M-15 gene in the chromosome. The chromosomal integration of the blaCTX-M-15 gene was mostly derived from the ISEcp1-targeting 5-bp AT-rich locus in the chromosome. The IS26-mediated chromosomal integration occurred when the upstream ISEcp1 from the blaCTX-M gene was truncated, targeting the anchor IS26 copy in the chromosome. Higher transfer efficiency of the blaCTX-M-15 gene-carrying FIA:R plasmid was observed in ST17 than that of the blaCTX-M-14 gene-carrying FIB:FII plasmid. The transfer efficiency of the plasmid differed by isolate among the ST307 members. The K. pneumoniae clones ST307 and ST48 harboring the blaCTX-M-15 gene in the chromosome were able to disseminate stably in clinical settings regardless of the environmental pressure, and the current population of K. pneumoniae blood isolates was constructed. Further follow-up is needed for the epidemiology of this antimicrobial resistance. IMPORTANCE Dominant F-type plasmids harboring the gene have been pointed out to be responsible for the dissemination of the CTX-M extended-spectrum-βlactamase (ESBL)-producing K. pneumoniae. Recently, the emergence of K. pneumoniae isolates with the blaCTX-M gene in their chromosomes has been reported occasionally worldwide. Such a chromosomal location of the resistance gene could be beneficial for stable propagation, as was the Acinetobacter baumannii ST191 harboring chromosomal blaOXA-23 that is endemic to South Korea. Through the present study, particular clones were identified as having built-in resistance genes in their chromosomes, and the chromosomal integration events were tracked by assessing their genomes. The cefotaxime-resistant K. pneumoniae clones of this study were particularized as results of the fastidiousness for plasmids to acquire the blaCTX-M gene for securing the diversity and of the chromosomal addiction of the blaCTX-M gene for ensuring propagation.

Original languageEnglish
Article numbere0045920
Issue number5
Publication statusPublished - 2020 Oct

Bibliographical note

Funding Information:
This research was supported by funds (2019ER540401) from the Korea Centers for Disease Control and Prevention. We thank Jong Hee Shin, Y. Uh, Jeong Hwan Shin, K. S. Shin, and Y. A. Kim for actively participating in Kor-GLASS to collect the K. pneumoniae blood isolates recovered in their hospitals.

Publisher Copyright:
Copyright © 2020 Yoon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Physiology
  • Biochemistry
  • Ecology, Evolution, Behavior and Systematics
  • Modelling and Simulation
  • Molecular Biology
  • Genetics
  • Computer Science Applications


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